Simultaneous vs. Staged Resection of Colorectal Cancer With Synchronous Liver Metastases

Colorectal Cancer Clinical Trial

— SYLMET  

Official title:

Simultaneous vs. Staged Resection of Colorectal Cancer With Synchronous Liver Metastases - A Multicentre Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06200831
• Other study ID #: 201644
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: December 31, 2031

Study information

• Verified date: April 2024
• Source: Oslo University Hospital
• Contact: Sheraz Yaqub, MD PhD
• Phone: +47-23073296
• Email: shya[@]ous-hf.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The SYLMET Trial is a randomized trial to compare simultaneous and two-staged resection of primary colorectal and synchronous liver metastases. This is an investigator-initiated, multicentre, randomized controlled trial to assess complications (primary endpoint), survival, cost-effectiveness, and quality of life (secondary endpoints).This trial will include patients with resectable primary tumour in the colon or upper rectum with less than five liver metastases that is possible to treat with surgical resection and/or ablation (RFA/MWA) at time of evaluation.

Description:

Colorectal cancer (CRC) represents the second most common cause of cancer and cancer death in Norway, and the incidence is increasing (Cancer in Norway, 2021, Cancer Registry of Norway). The liver is the most common site of metastasis from CRC. More than 4500 individuals are diagnosed with CRC in Norway each year, and approximately 20% of patients present with liver metastases at time of diagnosis (synchronous metastases). Resection of both the primary tumor and liver metastases is considered the only curative treatment, and has been shown to improve long-term survival, and is considered standard of care. However, the optimal timing of surgical resection of synchronous liver metastases in relation to the primary tumor is not well defined. Traditionally, staged resection has been preferred (i.e., resection of the primary tumour and liver metastases on separate admissions with a period of recovery between the two operations), whereas simultaneous resection is appealing (i.e., resection of both primary and metastases in one operative session). Despite a lack of randomized controlled trials comparing these two surgical approaches, the number of simultaneous resections has increased at several institutions. The evolvement of both liver and colorectal surgery in the last decades has led to reduced complications, making simultaneous resections more feasible. Previous retrospective cohort studies and meta-analyses suggest that simultaneous and staged approach carry similar postoperative complication and perioperative mortality rates as well as long-term survival. A recently published prospective observational study on staged or simultaneous surgery, reported similar outcomes in selected patients. To date, there is only one published randomized controlled trial which was aborted after inclusion of half of the sample size, after an accrual time of 10 years18. Due to lack of evidence, the majority of surgical societies worldwide still treats this patient group with staged resections, resulting in two hospital admissions, two rounds of general anaesthesia and surgery, and finally two episodes of postoperative recovery and rehabilitation. If this trial demonstrates that simultaneous surgery is safe, feasible, and cost-effective, it will potentially have a practice-changing impact worldwide.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2031
• Est. primary completion date: December 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age 18-80 years old.

• Both CRC and liver metastases in situ at time of evaluation.

• Resectable primary tumor in the colon or upper rectum.

• Less than 5 liver metastases, evaluated by the multidisciplinary tumor board meeting as possible to treat with surgical resection and/or ablation (RFA/MWA).

Exclusion Criteria:

• Unresectable primary tumor.

• Locally advanced primary tumor (T4).

• Primary tumor in the lower rectum with indication for abdominoperineal resection.

• Acute or imminent bowel obstruction.

• Perforation or major bleeding from the primary tumor.

• Pre-treatment of the primary tumor with a colon stent.

• Liver resection requiring resection of more than 2 adjacent segments (Couinaud).

• Liver metastases planned treated with irreversible electroporation (IRE).

• Non-resectable lung metastases.

• Metastases outside of liver (besides resectable lung metastases).

• Eastern Cooperative Oncology Group (ECOG) Performance status = 3.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Colorectal Neoplasms Malignant
• Liver Metastases
• Liver Metastasis Colon Cancer
• Liver Neoplasms
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Second Primary

Intervention

Procedure:
• Staged resection
Patients randomized to staged resection will be operated according to the decision made by the tumor board meeting (liver or colorectal cancer first, based on tumor burden and symptoms), but both resections have to be done within a time period of 4-12 weeks.
• Simultaneous resection
In cases with simultaneous surgery, the liver resection is performed prior to colon resection in order to keep a low central venous pressure during the first part of the surgical procedure and to avoid congestion of the anastomosis line owing to possible Pringle manoeuvre.

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo

Sponsors (6)

Lead Sponsor	Collaborator
Oslo University Hospital	Haukeland University Hospital, Helse Stavanger HF, St. Olavs Hospital, University Hospital, Akershus, University of Oslo

Country where clinical trial is conducted

Norway, 

References & Publications (3)

Kleive D, Aas E, Angelsen JH, Bringeland EA, Nesbakken A, Nymo LS, Schultz JK, Soreide K, Yaqub S. Simultaneous Resection of Primary Colorectal Cancer and Synchronous Liver Metastases: Contemporary Practice, Evidence and Knowledge Gaps. Oncol Ther. 2021 Jun;9(1):111-120. doi: 10.1007/s40487-021-00148-2. Epub 2021 Mar 23. — View Citation

Siriwardena AK, Serrablo A, Fretland AA, Wigmore SJ, Ramia-Angel JM, Malik HZ, Stattner S, Soreide K, Zmora O, Meijerink M, Kartalis N, Lesurtel M, Verhoef C, Balakrishnan A, Gruenberger T, Jonas E, Devar J, Jamdar S, Jones R, Hilal MA, Andersson B, Boudjema K, Mullamitha S, Stassen L, Dasari BVM, Frampton AE, Aldrighetti L, Pellino G, Buchwald P, Gurses B, Wasserberg N, Gruenberger B, Spiers HVM, Jarnagin W, Vauthey JN, Kokudo N, Tejpar S, Valdivieso A, Adam R; Joint E-AHPBA/ESSO/ESCP/ESGAR/CIRSE 2022 Consensus on colorectal cancer with synchronous liver metastases. The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE. HPB (Oxford). 2023 Sep;25(9):985-999. doi: 10.1016/j.hpb.2023.05.360. Epub 2023 Jul 13. — View Citation

Yaqub S, Margonis GA, Soreide K. Staged or Simultaneous Surgery for Colon or Rectal Cancer with Synchronous Liver Metastases: Implications for Study Design and Clinical Endpoints. Cancers (Basel). 2023 Apr 6;15(7):2177. doi: 10.3390/cancers15072177. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comprehensive Complication Index, CCI	The CCI is calculated as the sum of all complications that are weighted for their severity (multiplication of the median reference values from patients and physicians). The final formula yields a continuous scale to rank the severity of any combination of complications from 0 to 100 in a single patient.	90 days
Secondary	Health Economics	Cost-effectiveness calculated by incremental cost effectiveness ratio (ICER)	1 year
Secondary	Overall survival	Survival	3 and 5 years
Secondary	Clavien Dindo Complications	Scale from 1 to 5. Higher score meaning more severe complication.	90 days
Secondary	Quality of Life: EQ-5D	EQ-5D is an instrument which evaluates the generic quality of life developed in Europe and widely used. The EQ-5D descriptive system is a preference-based HRQL measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The scale range from -0.224 to 1; with 0, 1, and negative values corresponding to death, full health, and health states worse than death, respectively.	Pre-operative, 30-days, 90-days, 6 months, 12 months
Secondary	Quality of Life: EORTC QLQ-30	The EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) is designed to measure cancer patients' physical, psychological and social functions. The questionnaire is composed of multi-item scales and single items. Score from 1-100.	Pre-operative, 30-days, 90-days, 6 months, 12 months